Amplification of ESR1 may predict resistance to adjuvant tamoxifen in postmenopausal patients with hormone receptor positive breast cancer

The estrogen receptor (ER) is the target of tamoxifen, but endocrine therapies do not benefit all patients with ER positive tumors. We therefore hypothesized that copy number changes in the ESR1 gene, encoding ER, confer resistance. Within a consecutive series of ER positive, postmenopausal patients...

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Bibliographic Details
Published in:Breast cancer research and treatment 2011-06, Vol.127 (2), p.345-355
Main Authors: Nielsen, Kirsten Vang, Ejlertsen, Bent, Müller, Sven, Møller, Susanne, Rasmussen, Birgitte B., Balslev, Eva, Lænkholm, Anne-Vibeke, Christiansen, Peer, Mouridsen, Henning T.
Format: Article
Language:English
Subjects:
Aged
Analysis
Antineoplastic Agents, Hormonal - therapeutic use
Biological and medical sciences
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Cancer research
Cancer therapies
Chemotherapy, Adjuvant
Drug resistance
Drug Resistance, Neoplasm - genetics
Endocrine therapy
Estrogen
Estrogen Receptor alpha - genetics
Female
Gene amplification
Gene Amplification - genetics
Gene Deletion
Gene Order
Gynecology. Andrology. Obstetrics
Hormones
Humans
Mammary gland diseases
Medical research
Medical sciences
Medicine
Medicine & Public Health
Medicine, Experimental
Middle Aged
Oncology
Pilot Projects
Postmenopausal women
Postmenopause
Preclinical Study
Prognosis
Survival Analysis
Tamoxifen
Tamoxifen - therapeutic use
Tumors
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Description
Summary:The estrogen receptor (ER) is the target of tamoxifen, but endocrine therapies do not benefit all patients with ER positive tumors. We therefore hypothesized that copy number changes in the ESR1 gene, encoding ER, confer resistance. Within a consecutive series of ER positive, postmenopausal patients allocated to 5 years tamoxifen, we identified 61 patients with recurrence less than 4 years and 48 patients without recurrence at least 7 years after initiation of adjuvant tamoxifen. Archival tissue containing primary tumor was collected from 97 patients (89%). Tumor samples were analyzed for ESR1 copy number changes using FISH with a probe covering the ESR1 gene at 6q25 and a reference probe covering the centromere of chromosome 6. The assay was validated in a material of 120 normal breast samples. FISH analysis for ESR1 was successful in 91 patients (94%). Amplification (ratio ESR1 /CEN-6 ≥ 2.0) was observed in 11 of 50 (22%) patients with early recurrence, compared to two of 41 (5%) patients without recurrence. The difference is statistically significant ( P  = 0.033). In both groups, two patients with ESR1 deletion (ratio ESR1 /CEN-6 
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-010-0984-y